ABSTRACT Leukemia is the most common pediatric cancer affecting more than 40,000 children worldwide each year. During the last three decades, childhood leukemia (CL) incidence has increased in the US by ~35% overall, with an even larger rise among Latinos. This rapid increase implicates environmental factors in CL etiology, possibly in combination with genetic factors. Despite improved treatments for many types of CL, survivors remain at risk for serious complications. The role of environmental factors play in the development of long-term CL complications is unknown. The overarching objective of this proposal is to maintain, enhance, and enrich the infrastructure of two existing NIEHS-funded environmental case-control studies of CL conducted in ethnically-diverse populations of California (California Childhood Leukemia Study; CCLS, 1995-2016) and Guatemala (CRECER study; 2013- 2015). The CCLS has collected a wealth of environmental and genetic data, and assembled a rich inventory of biospecimens and dust samples for up to 2213 CL cases and 1310 controls, making it the most comprehensive CL study worldwide. The CCLS has produced seminal findings, documenting the prenatal origin of CL and identifying many factors that contribute to the development of the disease including: chemical exposures, diet, immune response, and genetic factors. CCLS also supported the development of novel laboratory methods for genome-, epigenome-, and exposome-wide studies of archived newborn dried blood specimens. The maintenance of CCLS resources and the enhancement of data sharing procedures are needed to efficiently expand ongoing etiologic and tumor-biology studies of CL and also to begin new studies on emerging research areas such as prevention, early detection, intervention, and survivorship. Our group has also completed a pilot study of CL in Guatemala that enrolled 50 cases and 50 controls in collaboration with established hospital networks, and collected biospecimens as well as genetic and environmental data with a focus on indoor air pollution. Maintaining these resources is critical to support future expansion of the study in this vulnerable population. In addition, the CCLS--45% of which is comprised of Latino children--and the Guatemala study will support future projects dedicated to identifying the causes of the ethnic disparity in CL risk. These studies will also continue to participate in the Childhood Leukemia International Consortium, as one of the select member cohorts from around the world that include children of Latin American descent. To achieve our goal, we plan to 1) curate and manage the inventory of existing biospecimens (e.g., bone marrow, blood, DBS, saliva, urine), dust samples, and data from medical records, interviews, geographic information system, and laboratory assays; (2) upgrade the biorepository and database capabilities, and (3) enhance data sharing by improving the relational databases used for timely data queries and project planning, developing a database for tracking requests, and designing a website for data sharing. In addition, we propose to enrich the CCLS by measuring novel biomarkers of in-utero psychosocial stress for which the impact on immune function and CL risk is unknown.